Effect of Liraglutide on Diastolic Dysfunction on Cardiac MRI in Type 2 Diabetes Patients

NCT02655770 | Completed Phase 4 DMC

• 1 other identifier: 2015-000410-22
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether liraglutide a GLP-1 analogue are effective in the treatment of diastolic dysfunction in type 2 diabetes patients analyzed by cardiac MRI. Secondary if the treatment has any effect on the perfusion of the heart on a cardiac-MRI.

Conditions

Diabetes Mellitus Type 2; Diastolic Dysfunction; Cardiac MRI; Myocardial Perfusion

Outcome Measures

Primary Outcomes (2)

• Change in diastolic properties as assessed by CMR.

  LA passive emptying fraction (%) (before and after glycopyrolate)

  Measured in week 18 and compared to baseline.

• Change in diastolic properties as assessed by CMR.

  LV peak filling rate (ml/s) (before and after glycopyrolate)

  Measured in week 18 and compared to baseline.

Secondary Outcomes (2)

• MRI indices of myocardial perfusion

  Measured in week 18 and compared to baseline.

• Echocardiographic indices of diastolic dysfunction

  Measured in week 18 and compared to baseline.

Study Arms (2)

Liraglutide arm

ACTIVE COMPARATOR

Patients will be treated with liraglutide (up to 1.8 mg s.c. once daily). Total treatment period will be 18 weeks.

Drug: Liraglutide

Placebo arm

PLACEBO COMPARATOR

Patients will be treated with placebo (up to equal to 1.8 mg drug dose s.c. once daily). Total treatment period will be 18 weeks. The study will be placebo-controlled with placebo as an add-on to conventional diabetes treatment. Thus, no patient will receive a sub-standard treatment.

Drug: Placebo

Interventions

Liraglutide DRUG

Also known as: Victoza

Liraglutide arm

Placebo DRUG

Placebo arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patient fully capable of informed consent
• Informed consent
• Age 18-80 years (both years inclusive)
• T2DM diagnosed at least 3 months prior to visit 0
• NYHA class I-III at visit 0
• E/e\* ≥ 9 or e\* (lateral) ≤10 cm/sec, or both
• LVEF \> 50%
• LVEDV/BSA \< 97 ml/m2
• Stable on heart medication for 6 weeks prior to randomisation
• Stable on antidiabetic treatment for 30 days prior to randomisation
• T2DM must be either treated with one or more oral anti-diabetic drugs or treated with human NPH-insulin or long-acting insulin analogue, alone or in combination with oral drugs

You may not qualify if:

• Lack of consent.
• NYHA class IV
• Type 1 diabetes mellitus
• Incretin-based therapy (GLP-1 receptor agonists; exenatide, liraglutide or other and DPP-IV inhibitors) within 30 days prior to randomisation (visit 1)
• Glitazon therapy within 30 days prior to randomisation (visit 1)
• Hypertension with inadequate blood pressure control: Systolic blood pressure \> 140 mmHg and/or diastolic blood pressure \>85 mmHg\*
• Supine systolic blood pressure \<85 mmHg measured at visit 0
• Significant valvular heart disease
• Hypertrophic cardiomyopathy, ARVC/D, non-compaction or amyloidosis
• Myocardial infarction, unstable angina, angina on exertion (≥CCS class 2) or coronary revascularization within 3 months prior to randomisation (visit 1)
• Hospitalisation due to incompensated heart disease within 30 days to randomisation (visit 1)
• HbA1c \>10% at visit 0
• eGFR\< 60 ml/min/1,73 m2 at visit 0
• Liver disease with aspartate aminotransferase/alanine aminotransferase \>3 times upper limit of normal measured at visit 0\*\*
• Hypokalaemia (P-potassium \<3.5 mmol/L) or hyperkalaemia (P-potassium \>5.5 mmol/L) measured at visit 0\*\*

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Slagelse Hospital: collaborator
• Novo Nordisk A/S: collaborator

Study Sites (1)

The department of cardiology, Rigshospitalet Denmark

Copenhagen Ø, 210, Denmark

Location

Related Publications (10)

• Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974 Jul;34(1):29-34. doi: 10.1016/0002-9149(74)90089-7. No abstract available.

  PMID: 4835750 BACKGROUND

• Factor SM, Okun EM, Minase T. Capillary microaneurysms in the human diabetic heart. N Engl J Med. 1980 Feb 14;302(7):384-8. doi: 10.1056/NEJM198002143020706. No abstract available.

  PMID: 7351930 BACKGROUND

• Nitenberg A, Paycha F, Ledoux S, Sachs R, Attali JR, Valensi P. Coronary artery responses to physiological stimuli are improved by deferoxamine but not by L-arginine in non-insulin-dependent diabetic patients with angiographically normal coronary arteries and no other risk factors. Circulation. 1998 Mar 3;97(8):736-43. doi: 10.1161/01.cir.97.8.736.

  PMID: 9498536 BACKGROUND

• Rodrigues B, McNeill JH. The diabetic heart: metabolic causes for the development of a cardiomyopathy. Cardiovasc Res. 1992 Oct;26(10):913-22. doi: 10.1093/cvr/26.10.913. No abstract available.

  PMID: 1486584 BACKGROUND

• van Heerebeek L, Hamdani N, Handoko ML, Falcao-Pires I, Musters RJ, Kupreishvili K, Ijsselmuiden AJ, Schalkwijk CG, Bronzwaer JG, Diamant M, Borbely A, van der Velden J, Stienen GJ, Laarman GJ, Niessen HW, Paulus WJ. Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation end products, and myocyte resting tension. Circulation. 2008 Jan 1;117(1):43-51. doi: 10.1161/CIRCULATIONAHA.107.728550. Epub 2007 Dec 10.

  PMID: 18071071 BACKGROUND

• From AM, Scott CG, Chen HH. The development of heart failure in patients with diabetes mellitus and pre-clinical diastolic dysfunction a population-based study. J Am Coll Cardiol. 2010 Jan 26;55(4):300-5. doi: 10.1016/j.jacc.2009.12.003.

  PMID: 20117433 BACKGROUND

• Yancy CW, Lopatin M, Stevenson LW, De Marco T, Fonarow GC; ADHERE Scientific Advisory Committee and Investigators. Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database. J Am Coll Cardiol. 2006 Jan 3;47(1):76-84. doi: 10.1016/j.jacc.2005.09.022. Epub 2005 Dec 15.

  PMID: 16386668 BACKGROUND

• Bhashyam S, Fields AV, Patterson B, Testani JM, Chen L, Shen YT, Shannon RP. Glucagon-like peptide-1 increases myocardial glucose uptake via p38alpha MAP kinase-mediated, nitric oxide-dependent mechanisms in conscious dogs with dilated cardiomyopathy. Circ Heart Fail. 2010 Jul;3(4):512-21. doi: 10.1161/CIRCHEARTFAILURE.109.900282. Epub 2010 May 13.

  PMID: 20466848 BACKGROUND

• Thrainsdottir I, Malmberg K, Olsson A, Gutniak M, Ryden L. Initial experience with GLP-1 treatment on metabolic control and myocardial function in patients with type 2 diabetes mellitus and heart failure. Diab Vasc Dis Res. 2004 May;1(1):40-3. doi: 10.3132/dvdr.2004.005.

  PMID: 16305055 BACKGROUND

• Nathanson D, Ullman B, Lofstrom U, Hedman A, Frick M, Sjoholm A, Nystrom T. Effects of intravenous exenatide in type 2 diabetic patients with congestive heart failure: a double-blind, randomised controlled clinical trial of efficacy and safety. Diabetologia. 2012 Apr;55(4):926-35. doi: 10.1007/s00125-011-2440-x. Epub 2012 Jan 13.

  PMID: 22246377 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Niels Vejlstrup, MD, Med.Sc.D

  Rigshospitalet, Denmark

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 12, 2016
• First Posted: January 14, 2016
• Study Start: February 1, 2016
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: January 14, 2021

Record last verified: 2021-01

Locations

DK (1)